Title: Suberoylanilide hydroxamic acid : a potential epigenetic therapeutic agent for lung fibrosis?
Authors : Wang, Z.
Chen, C.
Finger, S. N.
Kwajah M.M, S. d/o
Jung, M.
Schwarz, H.
Swanson, N.
Lareu, R. R.
Raghunath, M.
Published in : The European Respiratory Journal
Volume(Issue) : 34
Issue : 1
Pages : 145
Pages to: 155
Publisher / Ed. Institution : European Respiratory Society
Issue Date: 2009
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (publication)
Language : English
Subject (DDC) : 615: Pharmacology and therapeutics
616: Internal medicine and diseases
Abstract: Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novel in vitro evidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential. Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-β1 with or without SAHA. Collagen deposition, α-smooth muscle actin (α-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations. SAHA abrogated TGF-β1 effects on all the fibroblast lines by preventing their transdifferentiation into α-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of α-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations. Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis.
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific journal
DOI : 10.1183/09031936.00084808
ISSN: 0903-1936
URI: https://digitalcollection.zhaw.ch/handle/11475/12201
Appears in Collections:Publikationen Life Sciences und Facility Management

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